title: Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice.
abstract: Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned.
authors.affiliation: Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche, France. Electronic address: stephane.mouret@irba.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouret
authors.forename: Julien
authors.initials: J
authors.lastname: Wartelle
authors.forename: Sandy
authors.initials: S
authors.lastname: Emorine
authors.forename: Marine
authors.initials: M
authors.lastname: Bertoni
authors.forename: Nina
authors.initials: N
authors.lastname: Nguon
authors.forename: Cécile
authors.initials: C
authors.lastname: Cléry-Barraud
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dorandeu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boudry
mesh_terms: D000287:Administration, Topical; D000818:Animals; D020261:Arsenic Poisoning / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001152:Arsenicals / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003872:Dermatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004112:Dimercaprol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D004113:Succimer / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014835:Volatilization
chemical_list: D001152:Arsenicals; D002614:Chelating Agents; D004112:Dimercaprol; C035965:lewisite; D004113:Succimer
keywords: British anti-lewisite (BAL); Dimercaptosuccinic acid (DMSA); Lewisite; Skin lesion; Topical application; Treatment